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tv   Charlie Rose  PBS  August 17, 2012 4:00am-5:00am EDT

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>> rose: welcome to our program. tonight a special edition, the charlie rose brain series, year two. in our fourth episode we consider alzheimer's disease and frontal temporal dementia. >> it's hard to divide memory loss with age into two categories. it's called memory loss, normal aging or benign forget untilness and the dementias. now dementia that is most common is alzheimer's disease. what do we understand about these diseases. are they genes that have been identified that are important. are there many little genes having small effects or single genes that have some larger effects. we also want to understand how do we approach these things in terms of treatment. >> rose: episode 4 of the charlie rose brain series ii written by the simon's
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foundation coming up. understanding the brain. the series is made possible by grant by the simon's foundation. they want to advance research in the science.
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captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> tonight, we continue our exploration of the human brain looking at two of the most devastating diseases. they are alzheimer's disease and frontal temporal dementia, the central hallmark of alzheimer's disease is loss of memory, temporal dementia on the other hand is characterized by behavior and language dysfunction. boast are degenerative diseases
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taking a toll not only those diagnosed but everyone around them. patients are robbed of their independence, their relationship and their various identities. alzheimer's is the most common degenerative brain disease. more than 5 million americans visit. it is predicted by 2050, there will be three times as many cases. frontal temporal dementia or ftd is often misdiagnosed as alzheimer's. its effects are just as deaf staight. f. d is a colors of diseases that affect the region of the brain controlling language and decision-making. people undergo dramatic changes in their personality. some understand language. remarkably some patients can determine frefly unknown bursts of increase the creativity when brain areas decline and posterior regions take over. at the moment there's no cure or effective way to slow the progression of either
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alzheimer's disease or frontal temporal dementia but research has brought new insights into their diagnosis, pathogenesis and potential treatment. just a few weeks ago after this program was recording, two independent studies conducted by columbia and harvard were published that shed new light on how alzheimer's progresses. they indicate the disease can spread from brain cell to brain cell like an infection. dr. scott small is a coauthor of the columbia study. he appeared on the program on february 3rd to talk about these new developments. >> imagine three stages of alzheimer's. you do an autopsy find it in area 3. one with more progressive symptoms, he dies and you see alzheimer's in two areas and then three areas. that's always been known for the last 20 years. and the question has always been does area a jump to area b, jump to area c or are they just different areas that are vulnerable and they sort of pop in at different time points. that's a very difficult question
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to answer with human measures. and so what karen and i did, wd genetic engineering to produce alzheimer's in the area of a mouse and track changes over a period of time. >> rose: that's the pathway. >> that's the pathway it begins at the cortex. it's a subarea of the hippocampus. a circle very important for memory as you discussed in some of your brain series. so it starts in the hippocampus and then it spreads outside of the hippocampus and that might account for why when we do begn with patients as the disease progresses you start having other symptoms like language problems etcetera. >> rose: how does it go from one cell in one region to another cell in another region. >> that's interesting. we don't know that. we have theories. the big knows here is we show it does. it wasn't clear that it did and now that this has been shown now
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it really becomes an incredibly interesting question to ask exactly how does that happen. >> rose: as i noted earlier the nobody times story of the new developments on alzheimer's and my interview with dr. small ut s after the proam yre the tonight we show you this remarkable group of scientists who joined me to talk about where we are in understanding and fighting these devastating diseases. allison is a proifer ofenetic and psychiatry as well as professor in genetics and neurology at washington university in st. louis school of medicine. david is a jones professor and chair of neurology. imroos miller is professor of neurology and psychiatry at the university of psychiatry san francisco and once again my cohost is dr. eric kandel. he is as you know a nobel lawyer yet at the university and a howard hughes medical investigators. he gets our program off this
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evening telling us what it is we're about to see and talk about. we're full of stories of alzheimer's. people have been touched by it, their parents, somebody, their grandparents. we know there's something called age-related memory loss. how can we understand what we want to discover in this conversation? >> as you pointed out, it's very helpful to divide memory loss with age into two categories. what's called age-related memory loss, normal energy or benign senescent forgetfulness and the dementias. benign senescence forgetfulness like your muscles get weaker and stiffer so there's a weakening with age. this is in contrs to dementia which is a progressive much more
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serious disease. and it's impacts other aspects of memory storage. with normal aging, there's good news. as you're going to hear from david holtsman. >> rose: that's why i did it, see. that's exactly the reason. you once said find ways to challenge your brain. all of those people say i'm working too hard. take that. so this is very good news. in contrast, dementia for which he we have no cure at the moment is as you pointed out an
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epidemic. there are 5 million people that suffer from it right now. if you go by age, there are three or four percent of people age 70 have dementia. age 80, it's 20%. at age 90, 50%. it's just horrible. now, dementia that is most common is alzheimer's disease. in 1906, alzheimer's described a case that he said was unlike anything he had ever seen. a 51 year old woman came to see him. she had memory loss but had peculiar thoughts. she thought almost in a rational way, that her husband was complicated and she was getting very jealous of what he was doing. as time got on, she became suspicious of earth people as well. she thought they might be out to
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get her. her memory deteriorated even more. she began having difficult finding her way around her house. and after a while she had to be hospitalized. after five years of hospitalization she died. when she was autopsied, alzheimer did the autopsy. he found that three characteristic features that david and allison will describe characterize alzheimer's disease. there's a shrinkage of the brain, particularly the cervical cortex. there are plaque outside the nerve cell and also tangles within the nerve cell. many people think that this is the only dementia. as you pointed out, there are a number of other dementias. as well as frontal temporal dementia. decades before alzheimer described alzheimer's disease,
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arnold peak described it. in addition to memory loss if you have damage of the frontal lobe you have a disinhibition. people who never drank before will start to drink, those who never gambled before may start to gamble. if it spreads back to the temporal lobe, you get involvement of language as well. there are a number of things, particularly allison will have a lot to say about it. that is what do we understand about these diseases. are they genes that have been identified that are important. are they many little genes having small effect or single genes that have some larger effects. we also want to understand, how do we approach these things in
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terms of treatment, with mark here who is not only an outstanding scientist but actually a leader of gene tech has an experience of how to bring drugs to market. he can explain to us which is very difficult to understand why it's so difficult to bring a drug to market and why it's extraordinarily expensive. we're going to learn enormous amount. >> rose: let me start with david holtsman and talk about alzheimer's and also the difference between early onset alzheimer's and late onset. >> so a frequent question i often get from family members and patients is what's the difference between dementia and alzheimer's disease. really dementia is cognitive abilities that's sufficient to impair your function. alzheimer's disease as eric mentioned is one of several different disorders that cause dementia. the other common causes are
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strikes. dementia, kind of parkinson syndrome and frontal dementia which bruce will talk about. so really the difference between age-related memory loss and alzheimer's disease, while it's sometime difficult right when something starts changing to tell, is very common as people age, have some trouble with names, have a little slowing or thinking, have a little trouble with memory. but what's not normal is for someone to begin repeating themself to forget conversations, to have trouble with your checkbook when you never had trouble before. those are really signs of something that's wrong that's beyond normal aging. >> david you made an interesting point that if you worry very much about your memory loss, you're unlikely to have alzheimer's disease because you've got the insight that there's something wrong with your memory. >> right. a lot of people sometimes we worry about their memory and frequently we'll find that people that are really worried don't have alzheimer's disease. a lot of patients who develop alzheimer's have some trouble with their insight so they don't realize that they have a problem
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with their memory at all. >> rose: there's also this mental goods video. what does that tell us. >> so mel goods was the former ceo of warner lambert and he gives insight what it's like to start getting alzheimer's disease. that might be worth us watching. >> rose: let's take a look at that video. >> what do you do when you talk with your doctor? and your doctor says the following. the only words you don't want to hear. i'm sorry, you have late stage alzheimer's. not long ago, we had to confront this reality. i remember my first reaction. but doc, i feel fine. in fact, i feel great. and my first thought was, i'll beat this. and after all, i had a pretty
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good track record of beating the odds. at the age of 30, i became warner lambert's youngest ever country manager. i guess i caught some motives because after a spring of leadership jobs, i was asked to run the company. in 1991, i became chairman of warner lambert. we went from a company with practically nothing in the pipeline to the enterprise and invented what is now called selling medicine lipitor. remembering all the time i faced long odds and didn't blink. i wondered why can't i do that too. over a few days, the reality set in. alzheimer's disease is pitching a perfect game. i don't expect biomedical science to ride to my rescue.
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but i was a happy man. if we can change the course of this disease, with hundreds of millions of people who will soon be at risk. >> rose: what should we take from that? very powerful lesson that his eloquent testimony gives is that as of now, alzheimer's will win. >> i really think that the amount of discoveries the field has made over the last 30-35 years really give us hope that we will eventually conquer this. and even if you look back at what alzheimer first showed 100 years ago in the slide, he described these classic lesions that we all talk b amyloid plaques and neuro fibular tangles, you can see what's called an amyloid plaque which consists of a protein and then the next arrow you can see a
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neuro fibular tangle. these two leagues at first were thought just -- lesions were first to be by-products of the disease. they are fundamentally involved in the cause of the disease which we'll talk more about as we go along. one of the fascinating things about these lesions we've learned is they don't start forming in the brain when you first develop memory loss. they actually start about 15 years or so before you have any change in your memory or anything. i think that in and itself if e detect these things we may be able to prevent ultimately the damage to the brain. you can see that these lesions, these amyloid plaques and tangles don't form all over the brain. they actually form in very specific areas so you can see that the amyloid begins to build up in parts of the brain called the free frontal cortex which is involved in problem solving. and you can also see it build you that temporal parietal cortex which are regions
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involved in memory, connected in memory areas. and when this first builds up the brain's able to compensate and there's quite a bit of reserve the brain has so that people seem fine for a while. you can't tell the difference from somebody who has these lesions initially and not. but then over time as more and more damage builds up in the brain, you can see that the brain begins to shrink because the nerve cells and their connections are being lost and damaged. and regions like the hippocampus, which is very important for memory just gets very small as the nerve cells are gone. and so i think what we really learned, that's sort of what a pathologist is seeing under a microscope you can now see these things with imaging. what we've learned a lot about in the last 25 years is really the underlying science about this desire. and while we certainly don't know everything, we do have a lot of insights that the field has made. for example this amyloid protein which accumulates in the brain
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of people with alzheimer's disease as shown in red, we know it's derived from a much larger protein called the amyloid precursor protein which sits inside the cell membrane. a lot of interesting science went around figuring out how is it that this amyloid data protein, the red part of that figure actually gets separated from the amyloid precursor protein. it was figured on other there's enzymes ones called bay autopsy that makes that cut and another one called the gamma cut such that these enzymesally the amyloid protein from the larger protein and forms the amyloid protein or abeta. this is made bay all -- by us all the time. what starts is this soluble protein that floats around clumps up and it forms clumps.
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they become toxic. that's a major theory that appears to be the case in alzheimer's disease. another protein that's inside the cell called tao, it's soluble it can clump up and aggregate. the combination appear to play an important part in the progression of the disease. >> rose: let me turn and talk about the genetic consideration here. >> what we've learned about the disease, which is actually that there's, looks like a single common pathway of disease. so these genes, the amyloid precursor protein which david mention and two other genes, people can have mutations in these genes that cause the disease. what we understand is these
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mutations lead to aggregate, increased production of that abeta fragment that david was talking about. so that seems to be the earliest change that we can find in these people is really pinpointing the amyloid protein as being central to the disease. >> rose: where is the focus of the genetic research. >> right now? so right now, most of the research is on understanding risk factor for the rests of the cases, the 99.9% of cases. >> it's a single gene defect. >> exactly. they are likely to be caused by many genes a very small effect and also potentially the environmental factors may play some influence in co-morbidities, other people may have increase risk.
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but all of these findings have actually pointed to this amyloid pathway, so whatever is the proximal cause of disease, it all filters into the same pathway that affects aggregation of this amyloid peptide and ultimately loss of cells and dementia. >> we don't know for certain whether this is, you know, the ultimate truth as you pointed out but it's a very powerful hypotheses that has been extremely useful in research and it's very reassuring. because in other diseases that were discussed like schitzophrenia or depression, you can't point to a single gene that can do it for you. so it's lots of little genes that seem to be responsible. and to figure out how those kinds of diseases work is much more difficult. so even though the progress at the moment seems to be very slow, our understanding of it has been really amazingly rapid.
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>> we were able to make animal models in fact of the disease by taking these very genes and mutations and introducing them into a mouse. before that though there really was no small animal model of disease and so it made it extremely difficult for scientists. >> rose: explain what happened when you introduced them into the mouse. >> as the mouse ages, there are changes in the brain that lead to aggregation of the same protein in the brain as you see in humans. and in some of the mouse models, there's some suggestion they also be some changes in memory in these animals. it's not a perfect representation of the disease. >> the representation is that the mouse only lives to be two years old while alzheimer's as david pointed out, you don't even see anything until the
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disease -- >> rose: for years. so the majority of the cases come after 65. >> right. so we encourage in the animals, we have to see some early aspect of the disease is going on. they show some cognitive deficits. so it's very encouraging; is that right let me turn to bruce and talk about the differences of temporal dementia. >> most people have never heard of frontal temporal dementia and that's because we didn't know much about it until recently. even the neurology textbooks say don't pick this disease because they thought it was so rare and they thought we couldn't separate it during life and alzheimer's disease. we've learned now it's the most common cause along with alzheimer's disease for dementia and people under the age of 64, and continues to be a significant presence easement as we get over 65. so very common in people who are young who have a dementia. as allison will talk about, we know a lot about the genes now
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that cause this, they are different genes than alzheimer's disease and also different proteins that aggravate the brain. for me it's one of the most fascinating diseases imaginable. it begins in parts of the frontal lobe, very small areas that are involved with our social intelligence, our ability to inhibit impulse speech affectate. what you see is profound disorder of social behavior, moral reasoning. you see people who are never disinhibited committing anti-social acts. going into stores, taking things. we did a study where we found about half of our patients early in the illness either were arrested or could have been arrested doing something they did associated with this illness. another fascinating thing about
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this disease is it hits the part of the brain that allow us to relate to others to empathize and empathize with other people. >> rose: the right side. >> that is the right side, absolutely. you see these people who were once loving who become cold and different to people around them. they become addictive, they over eat, they begin to smoke when they never smoked before. so this is really a profound social disorder that has a huge impact on a family. it hits people when they're younger so these are often people who are working at a critical point in their life. i would say often, if not always, we see people make bad judgments around their finances. sometimes they become bankrupt. often become alienated from their loved ones. >> rose: are there specific genes that contribute? >> yes. i think like alzheimer's disease it offers a great hope for treatment. >> rose: let me come back allison and tell me about the
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genetic composition. >> from the genetics what we discovered was in contrast to alzheimer's disease where so far all the evidence have pointed to a single common pathway. what we've discovered about frontal temporal dementia is that it's many diseases that as you can see that we actually identified three different genes, but they cause a similar clinical disease but the pathology will look different and the genes that are altered are different. and so we have parallel pathways where you have a clinically similar looking disease but very different underlying causes. and so that has big implications for the point of view of your freemont where alzheimer's disease one might expect if you can modify that central pathway that is the person in all of these diseases, you might be successful with a treatment
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that's targeting that. or as in frontal temporal dementia, it's probably multiple diseases and we will need, we'll need to understand which form of frontal dementia an individual has before thinking about treatment because the treatment could be quite different. >> rose: before we go further, tell me the definition of dementia. >> dementia is a loss of memory in aspects of cognitive function. the duration of cognitive function. >> rose: loss of memory. >> it's more than memory. it's aspect of cognition. >> it needs to interfere with your social and occupational function. so it has to be enough that it affects your daily life. >> rose: let's move to where you are in terms of some of the basic science in looking at the discovery of marketable and safe products. >> maybe i can talk about progress in identifying drugs for alzheimer's which are most
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advance but later in the conversation perhaps we can come back to frontal dementia and other things. there are a few drugs already approved for the treatment of alzheimer's but they provide modest benefit. they work by boosting the function of nerve cells that remain to provide some benefit in terms of brain function but it's usually temporary because they don't target the underlying cause. neurocells continue to die, the brain continues to deteriorate. so while they can help some patients somewhat, they don't make a big dent in the disease. what we need of course are drugs that slow or block progression of the disease by targeting the underlying mechanism. now unfortunately, several drugs that attend to do that have failed and none have so far been successful. but what many are pinning their hopes on are drugs that target this amyloid cascades that allison and david discussed. and more specifically that abeta peptide the one that aggregates
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and forms plaques. based on the assumption that data and small aggregates are bass actors that derive the disease and have to be stopped. now, it's taken a long time to develop drugs for the target abeta. drug discovery of course is inherently a lengthy costly and risky business. what you can see here is on average it takes about 14 or 15 years and about a billion dollars to make a drug. and the attrition is just massive. so when you start with about two dozen projects trying to make drug candidates, only about a dozen drug candidates will come from that. only about nine of them turn out to be safe enough to enter human clinical trials and only one, one of nine will make it all the way through to approval with the others failing either because they proved to be unsafe or because they just don't work. in the case of alzheimer's disease, there's a further hurts which is there's a protective barrier that prevents most drugs from entering the brain so you
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have to get around from that as well. it's taken a long time to make drugs for abeta which was discovered over two decades ago. it took almost a decade to figure out an approach to enable us to get access to abeta in the brain. but the good news is that applying that approach, there are now about half a dozen drugs in clinical trials, some of them in late stage clinical trials. some have already shown they can reduce the amount of plaque in the brain of alzheimer's patients. in this calendar year in 2012, we should see the clinical results for at least one of them with results of others giving relts in subsequeea>> if that ds satisfactory, what are the results. >> the result is a slowing cognitive decline. >> rose: it's not that you can reduce the impact already of the decline or the erosion or destruction. >> there are loss of nerve cells and you can't get them back. >> rose: there's no regeneration or something like
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that. >> there's some regeneration of never cells but not in those s ofregionhe brain o most ons of the brain. excuse me marc there's another hopeful side that you mentioned before and that is we're also improving techniques to detecting the disease earlier so the combination of new insights to be therapeutically and getting at the disease earlier and ways of having mark in the blood. >> that's an important point eric. i think one of the scientist biggest concern with the ongoing trials is patients are already symptomatic. as david mentioned earlier, those patients have had the disease progress in the brain for years. are arguing that we should be doing the trials in patients who are presymptomatic based on the use of new biomarkers that enable you to detect the disease even before the symptoms appear. david is a world expert on this and perhaps could comment on it. >> if you think of alzheimer's a
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little bit like cardiovascular disease we know the plaques that build up in the heart that block the arteries take many years to build up. and some of the most effective treatments now to prevent a heart attack or stroke is to take medications that lower cholesterol. you get that checked. we now have markers for alzheimer's disease that tell you that the changes of alzheimer's are occurring in the brain while you're still cognitively okay. some of those are imaging, some of them are checking the fluid in either the flood or what's worked the best so far for spinal fluid, we can really tell that somebody is likely going to develop alzheimer's disease in the next few years. i think if things like that are applied in clinical trials, maybe we'll actually be able to give things to actually delay or even prevent the disease. and i think that's where the big hope is. >> rose: so that if you are successful in doing that you see it maybe after it's only five years into development or ten years into development. >> exactly right. >> there's good evidence we can do that now.
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>> rose: so what's necessary to advance that. >> in theory, it's straightforward. you enroll a lot of normal people of a certain age and you assess these biomarkers and then you put them on a treatment or placebo and you see if it delays the disease. the problem is it takes many years for somebody to progress even if they are going to develop disease it might take three, four five six years. and so it's going to be very expensive to do these trials and how even a single pharmaceutical company might be very difficult for them to do that. so we may need to come up with new models. maybe public private partnerships or other new ways to be able to enable us to get a treatment. i think that really is the way to go though. >> or find markers so that you go early before symptoms appear and you give the drug and you measure outcome not based on the development of alzheimer's disease per se but further progression, presymptomatic progression of the disease. >> just like cholesterol in your
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blood. you give a drug and see if it gets lower. this same type of thing could occur in alzheimer's disease. >> rose: we move this over where you are. >> with tell moral -- temporal dementia has given us exciting genes. we've learned that people about 5 percent percent with frontal temporal dementia carries this gene. it's something called insufficiency which just means we don't get enough pro gran lynn from the blood and brain or figure out a way of delivering this protein. so it becomes one of the simplest neurodegenerative diseases. we're already beginning to think about treatment trials with drugs that we think will elevate the progranulynn levels in the blood and brain. >> rose: talk about tort of
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the creativity in the left-sided damage there and what that tells us. >> yes. so 1996, i started to notice that some of my patients all had a progressive aphasia. they had the left frontal part of the brain or the lefttempora. thessive language disorder, began to show visual creativity. and this is i think a fascinating story about the brain. it tells us that we have circuits and we turn one off and we may actually be turning other circuits on. and i think in some of these patients there's actually increased activity in the posterior parts of the brain that on the right side that are involved creating art. i would like to talk a little bit about ann adams who i think was our most extra exordinary
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experience. her and her husband who was a mathematician and ann was a biologist that studied the epithelium of the ovary under the cell and decided she didn't want to work in science and she began to create art. what ann did initially was some static pictures she hadn't used a paint brush very much. but then i think her work built and it became more visually beautiful. >> she became obsessive about this. all she wanted to do was grow to the art studio and look at i've forgotten who it was and that was her life which is extraordinary. so scientist becomes more committed to art than she could ever have imagined. >> yes. her whole life became art and painting. >> rose: because it moved to a different section of her brain. >> we think so. beoreverpederure of ann's ai language disorder and we saw that already she was showing loss of tissue. and this is, she had lossof tissue initially in the left part of the brain involved in
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producing speech with a larger posterior parietal area which we think was involved in this burst of visual creativity and it was the beginning of the frontal temporal dementia. i wanted to talk about this of ann's which she said unraveling it. what she attend to do was capture in a visual way what bolero does and bolero is a very rhythmic repetitive compulsive piece. very similar i think to the way ann approached the art. and. >> rose: she did it note by note. >> she did it note by note. she took this 340 meter piece that is highly repetitive with a progressive crescendo and she began initially with the beginnings of this and showed in a snaky fashion how the crescendo builds. if the note is longer, that
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means that bolero was producing a louder note, if it was wider, they played the note longer. what you see here is a sudden change in key which ann adams was fascinated by. we go from dull blue and keys to this gawdy fluorescent pink and orange, which is the beginning of the crescendo and the op of the music. ♪ and so ann have done something we called transmodal association. she associated sound, rhythm, auditory processes with a visual picture. >> rose: this is the beginning of the onset. >> this is the beginning --
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absolutely. and the amazing thing for us, we don't think it's a coincidence that ravel, himself, seven years before he produced bolero was beginning to have problems with writing. and he developed a progressive aphasia we think identical to ann's. seven years before ann was diagnosed with progressive aphasia she produced this wonderful piece. of course neither of them knew about the other. >> rose: let me tie up this idea of the genetic disorder but some kind of environmental impact. >> right, yes. so probably the well described example of how environment can play a role, relates the most common risk factor for alzheimer's disease which is a particular form of protein called lipo protein e or apo
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protein for short. this protein comes in three forms, two, three and four, not one. and so the three is the most common form. and that has no, are that is neutral in terms of risk. the apoe4 form of this protein increases our risk for having alzheimer's disease and this will increase one's risk for alzheimer's disease. what is being observed is if you have head injury with loss of consciousness, if you have an e4 form of the protein, your outcome is much worse than if you have one of the other forms of the protein. so this is an example of where an environmental factor head injury can have a different
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impact on your risk for disease depending on earlier underlying genes. and it's really quite a substantial increase in risk. so people who have the apo e4 form of the protein and have a head injury can have a 15 to 20 fold increase in risk of developing alzheimer's disease. >> rose: go ahead. >> i'm going to say, exactly, this has a big impact when you think about the sports that people play where you contact sports where -- >> rose: concussion seems to be on the rise. >> exactly, that's right. i mean i think that this is, has significant public health issues when you think about the number of people who are obviously at risk, putting themselves at risk for developing alzheimer's disease or other dementia. >> rose: before i open this up to broader questions, talk finally about drugs and what we've learned the fact that if the drug fails does not mean
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that there are not lessons to be learned. >> that's right. we've already discussed how even the ongoing trials right now to target this abeta peptide, if they fail is it because the theory is incorrect or is it because we intervened too late. has the horse already left the barn and closing the door won't keep it in. so through these trials we will see effects on amyloid, we'll see whether there's behavioral improvements and improvement in cognition. we'll be able to learn how good art theory is and i think that's one thing that's going to happn over the next several year. as we target one specific mechanism there, i think it's very important that we continue to target other mechanisms. one of the great lessons of drug discovery is it's rarely the case hitting one mechanism you can get all the benefits you want. you can get a magic bullet. typically you need combinations of drugs hitting different
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aspects of the mechanism. i think a very important area in every generation in general is understanding once the disease is initiated with factors like abeta or progranulin how does the death get executed, the executioners of the nerve cell death we heard that protein wered about earlier is involved. so drugs against are being made and developed. we'll get more entry pointed for drug development that can work in a fashion to the other drugs. >> rose: when we look at the concentration of tao what do we find. >> we see it increasing as in spinal fluid for example, it increases over time as the disease progresses. tao is interesting because it's in those tangles that david talked about initially in alzheimer's disease, it increases in the spinal fluid. you may have noticed on allison's chart in frontal
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temporal dementia -- these execution pathways gets drugs that works across dementias. they may start for different reasons but they macon may con. >> rose: let's talk about the following, the cost of this. there are huge societal costs. >> enormous. these costs are true for cancers. it takes a long time to bring a drug to market. the reason that brings us to enormous here is because this is an epidemic. so many people suffer from it. >> rose: because people are in old age. >> when i was a medical student, this was not talked about. this is a disease of the last 50 years because people are liferring a significant amount longer and dramatic increase. >> rose: when you were in medical school there was no
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discussion of alzheimer's. >> practically not. >> me neither. in terms of societal costs currently the alzheimer's association reports that the cost to society today or in the united states alone is about $280 billion a year and that's where money changes hands primarily through nursing care. and it doesn't involve in kind care from families. it's estimated as david said there's going to be a trippling of the population by 2050, it's estimated the cost of a nation in today's dollar will be a trillion dollars a year. we're trying to squeeze a trillion dollars out of the next decade. it shows you the magnitude of the economic impact not to mention the human toll. >> i think the country's beginning to realize this is a national effort. and the government's actively becoming involved in it. there are plans that by certain dates hopefully we'll have significant progress on this. >> rose: there are a lot of great questions for government
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in the 21st century the cost healthcare is a percentage of the gdp and how to make more effective and more efficient healthcare treatment and the delivery of healthcare. >> it's fascinating. he's such an amazing guy. he reminds me a little bit of president reagan who also came public with it realizing it's not going to do much good for him perhaps but people will now what how important the disease is. mel's company is the first company trying to develop drugs. >> rose: right. i always thought that reagan's decision and the eloquence of what he said about alzheimer's and the way he said it was one of the significant contributions that he made. >> absolutely. >> rose: in a sense. bringing the prestige and bringing attention and recognition. >> not being embarrassed by it.
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>> taking the stigma away. >> this is a disease, it is not bad behavior. >> rose: exactly right. >> one of the real tragedies now is that we had a spokesperson at that time. we don't really have a spokesperson at the moment for alzheimer's disease. suddenly we have these incredibly powerful biological approaches that we think are poised to make a difference for our society and we're not getting the nia funding. >> rose: you're worried there's opportunity that we may miss the chance to activate. >> exactly. >> we finally have the discoveries. now we need to act and get treatments that are effective. >> rose: the need is so large that they can provide the kind of resources necessary. >> that's true although there has to be more things than that as well. >> yes. the government has to be involved. it's such a large size. what is tragic is that the cut back in government spending, research is being hit.
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we're fortunate that people like the lauders are interested in alzheimer's disease and that's where it has drawn attention to it. it's a philanthropy but it can never substitute for what the government can do. >> rose: i'm not clear because we hear all the time we should be doing things to make our brain more active. i'm not sure that i understand what is the hard empirical evidence of doing that. >> if you keep your mind active and actually being in good health, keeping blood pressure under control, keeping diabetes under control. these are protective factors against age-related memory loss. so age-related memory loss is something we can do something about. this is the question of getting the word out. >> rose: as we have made very clear here and everybody knows more and more you meet people that have in some way been connected to either some kind of dementia or whether it's alzheimer itself.
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so we are aware here in terms of the research and the possible break throughs in the near term. let's take a moment. >> i think we really understand a lot, not everything about what under lies the disease. and we are at a point where new treatments that are being developed now are in people for the first time that really attack the mechanism. and we're probably going to have to also treat earlier. and that's where there's real hope to really delay or prevent the disease and that should happen in the upcoming 10, 15 years. >> could you summarize some of the markers available. >> some of the markers for the disease include being able to image amyloid in the brain of a living person. you can also see markers of amyloid -- >> rose: you can do that now. >> we can also in the spinal fluid detect when the brain is beginning to degenerate markers like tao. combining these thing together you can detect roughly when somebody's likely going to develop the disease. >> i think it's worth pointing out that the progress has been
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very exciting in terms of the basic science and even more exciting seeing it more more towards clinical experimental drugs. there's many thing we don't know for example how it is the nerve cells were actually dying which if we knew it would enable the next generation of drugs. as we move forward with the current drugs coming in the years and decades we need to keep track. >> rose: we do not know why the nerve cells are dying. they are dying we don't know why. >> in terms of the why, they're the dying because of the triggers at the top progranulin bay thank you and other things. we don't know how they get dismantled, what's the program of suicide inside the nerve cells at the biochemical level. if we knew that we could intervene and block it. >> rose: how far away do you think we are from that just to ask a locker room question. >> you never want to make a prediction in science. but if i had to make one i think we're poised to make a lot of progress in coming years because a lot of insight into how cells
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die arisen over the most decades that are converging on an understanding. >> he makes a very good point which we made repeatedly here. the brain is a marvelous organ and we like to think that we understand it completely. we're extremely far from doing that. it's obvious. and this is even more true in terms of treatment. these are extremely difficult problems. and it's going to take a long time to really tackle them. but one has to realize that molecular biology wasn't a applied to the brain until 1980. the imaging techniques, we were house offices, x-rays, the most primitive techniques of visualizing and you didn't really visualize the brain you visualized the vasculature, you visualized the bones. you didn't visualize the actual brain until brain imaging and scanning. that's what, 30 years. >> rose: i'm always struck no matter how sophisticated the science and biochemistry and
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whatever it is, it is always very fundamentals. unless you understand why the nerve cells are doing that, you can't even go to understanding how to address the issue. >> that's right. >> rose: let me do something we always do here. results.ntestingf y havel a i you whais the st important queon that you'd lke to s awered? >>mp mstta questoni'd like to see answered is how it is that the nerve cells die in these diseases. >> i really wanted to know if you treat the disease with these really attractive mechanism-based therapies, whether u delay the disease. delay the onset of the disease which would be effectively preventing it. >> rose: and you're optimistic. >> i'm very optimistic. >> rose: in the near term? >> i think in the next 10 to 20 years. >> rose: that's near term. >> i spent 30 years working on diagnosis and i don't want to work on that, i think we're good at it now. i want to spend the rest of my time showing we can treat
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frontal temporal dementia. >> rose: today. >> today. this is going to be like cancer. we're not going to treat all cancer at the same time, we're going to pick off different subtypes of frontal temporal dementia, alzheimer's disease one by one. about identified think progranlin and relayed problems of std i think we are making some head way. >> yes. i would agree with dave, and i think that maybe a combination of knowing our genetic background and genetic risk factors in combination with these biomarkers is really going to be something that will allow us to identify people who are at most risk at the earliest possible times to allow the treatments to be used to prevent disease rather than to be curing the disease. >> rose: memory's your game. >> i have nothing to contribute. my thing is memory. and what i like is bruce's finding that there's a
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decreasing creatively in some patient with damage to the left hemispheres and frontal temporal dementia. that is so profound because there's an idea that one of the families of neurology says the left hemisphere inhibits the right hemisphere. if you remove that the right hemisphere which is more creative emerges. we've seen this. the various diseases release certain place tice tease. >> rose: thank you very much. great to see you again. thank you. captioning sponsored by rose communications captioned by media access group at wgbh access.wgbh.org
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